tbuckley/cabot-search huggingface dataset:
AB0111 EFFECT OF TOFACITINIB AND GLUCOCORTICOIDS ON INTESTINAL PERMEABILITY, EPITHELIAL DAMAGE AND BACTERIAL TRANSLOCATION IN RAT ADJUVANT-INDUCED ARTHRITIS
Authors: S. Hecquet, P. Totoson, M. Tournier, C. Prati, D. Wendling, C. Demougeot, F. Verhoeven
Journal: Annals of the Rheumatic Diseases (2022)

Background Growing evidence indicated that the intestine is not only a target but also an actor of the pathogenesis in chronic inflammatory rheumatic diseases (CIRD). Consistently, increased intestinal permeability (IP) and damage (ID) as well as bacterial translocation (BT) have been described in patients with CIRD. However, the effects of treatments used in patients with CIRD on gut health are unknown. Objectives To determine the effect of glucocorticoids (GCs) and tofacitinib on IP, ID and BT in rats with adjuvant-induced arthritis (AIA). Methods AIA was induced in 6-week-old male Lewis rats by a tail injection of Mycobacterium butyricum in incomplete Freund’s adjuvant. At onset of arthritis, rats were treated daily with prednisolone at low (0.1 mg/kg/day, i.p.) or high dose (10 mg/kg/day, i.p.), or with Tofacitinib (10 mg/kg twice a day, s.c.) or with vehicle. After 21 days, IP, ID and BT were assessed by measurement of plasma levels of zonulin, intestinal Fatty Acid Binding Protein (iFABP) and serum levels of soluble CD14 (sCD14) by ELISA), respectively. Arthritis severity was daily evaluated through the determination of an arthritis score. Results Compared to vehicle, Tofacitinib and high-dose of GC both reduced arthritis score (p&lt;0.001) and levels of sCD14 (-44%, p&lt;0.001 and -41% p&lt;0.001 respectively) in AIA. High dose of GC decreased iFABP (-17%, p&lt;0.05) levels but had no effect on zonulin levels. Tofacitinib did change nor iFABP neither zonulin levels. As compared to vehicle, the low-dose of GC had no effect on arthritis severity, sCD14, iFABP and zonulin plasma levels. Conclusion Prednisolone at a dose efficient on arthritis did not worsen but on the contrary reduced intestinal bacterial translocation and epithelial damage. These results are consistent with the positive effects of GCs on intestinal dysfunction observed in case of sepsis or colitis. The lack of efficacy of the sub-therapeutic dosage of prednisolone suggested that effects of GC are, at least partly, related to their anti-inflammatory effects. Consistent with the positive effect of jakinibs in patients with inflammatory bowel disease, Tofacitinib blunted intestinal bacterial translocation in AIA. Given the suspected pathophysiological link between bacterial translocation and arthritis, our results identified a new mechanism involved in the positive effects of GC and tofacitinib in arthritis diseases. Disclosure of Interests None declared
AB1226 AUTOLOGOUS MOSAIC OSTEOCHONDROPLASTY IN THE TREATMENT OF TALAR OSTEOCHONDRAL DEFECTS
Authors: T. Omelchenko, O. Burianov, A. Liabakh, E. Levitskyi, O. Turchin
Journal: Annals of the Rheumatic Diseases (2022)

Background Osteochondral defects of the talus (ODT) is a relatively rare, mostly traumatic pathology, in 6.5 % of cases complicate the course of inversion and eversion injuries of the foot and ankle [1]. Objectives To conduct a clinical analysis of the effectiveness of autologous mosaic osteochondroplasty in the treatment of patients with osteochondral defects of the talus on the basis of determining the dynamics of pain and restoring the amplitude of ankle movements. Methods The study included 34 patients with post-traumatic osteochondral defects of the talus (27 men, 7 women, mean age 24.8 ± 2.1 years) who underwent osteochondroplasty. The duration of painful clinical symptoms before osteochondroplasty ranged from 4 to 18 months. Functional treatment outcomes were assessed over a period of 12 to 36 months using the International Foot and Ankle Surgery Scale (AOFAS), pain dynamics were assessed using the Visual Analog Scale (VAS), and ankle movement recovery dynamics were determined. Results Osteochondral autologic grafts were removed from the lateral condyle of the ipsilateral femur. Defect sizes: square from 82 to 129 mm 2 (110,3 ± 0.8 mm 2 ), depth from 7 to 16 mm (12 ± 0,8 mm). Incorporation of the graft in the recipient bed occurred within 1,5 – 3 months. Long-term follow-up was 12 – 36 months (22,8 ± 3,8 months). The level of pain was decreased from 5,7 ± 0,3 before to 0,9 ± 0,3 after the operation (p &lt; 0.001; paired t-test). Improving of foot function according to AOFAS scale (hindfoot section) was established from 64,9 ± 1,4 to 95,9 ± 1,1 (p &lt; 0.001; paired t-test). Extension increasing from 15,0 ± 0,9 to 18,4 ± 0,7 and flexion increasing from 22,9 ± 1,2 to 30,7 ± 1,1 was registered. There were no cases of implants failure or their instability neither the increasing of degenerative changes in the ankle joint. Conclusion Osteochondroplasty is the effective method of congruity restoration in cases of post-traumatic talus osteochondral defects, promotes a significant reduction in pain syndrome and an improvement in the function of the ankle. The unknown mechanism of the analgesic effect of osteochondroplasty requires further research. References [1]O’Loughlin PF, Heyworth BE, Kennedy JG. Current concepts in the diagnosis and treatment of osteochondral lesions of the ankle. Am J Sports Med. 2010;38:392-404. doi: 10.1177/0363546509336336. Disclosure of Interests None declared
POS0718 SIROLIMUS MONOTHERAPY FOR THROMBOCYTOPENIA IN PRIMARY ANTIPHOSPHOLIPID SYNDROME: A PILOT STUDY FROM A TERTIARY REFERRAL CENTER
Authors: W. Xie, L. Ji, Z. Zhang
Journal: Annals of the Rheumatic Diseases (2022)

Background Thrombocytopenia (TP) is considered as a warning sign of high-risk antiphospholipid syndrome (APS) and sometimes a paradoxical sign of anti-thrombosis treatment. Currently there is an extreme paucity of effective and safe drugs for long-term management of TP in primary APS patients. Objectives We aimed to explore the efficacy and safety of sirolimus monotherapy. Methods In this real-world study, we included 7 consecutive patients with primary APS who received sirolimus monotherapy for TP. Oral sirolimus was initiated at a dose of 1-2 mg once daily and then adjusted primarily based on clinical efficacy and tolerance, with consideration of sirolimus trough concentration of ≤15 ng/ml. Results Of included patients, the median age was 58 years with median disease course of 1.5 years and 4 patients were treatment-naïve. All patients completed 6 months of sirolimus therapy with median follow-up of 6 months (range: 6-15). All patients received sirolimus monotherapy for TP during entire follow-up, without adding any additional agents. Overall, platelet count exhibited substantially increasing trend after sirolimus administration during the first six months (p&lt;0.001) and being stable later. Specifically, median platelet count was significantly increased from 59×10 9 /L before sirolimus to 90×10 9 /L at month 1 (p=0.028), 131×10 9 /L at 3 months (p=0.028) and 178×10 9 /L at 6 months (P=0.018). Overall and complete response were respectively achieved in 6 (85.7%) and 5 (71.4%) patients at month 6. Importantly, overall response was achieved in all 4 treatment-naïve patients. Additionally, there was different extents of decline in the titers of antiphospholipid antibodies after sirolimus treatment. Regrading safety, only one patient experienced elevated cholesterol level with recovery after atorvastatin treatment. Conclusion Sirolimus monotherapy confers good efficacy and tolerance for TP in primary APS patients, and therefore may be considered as a first-line therapy. Figure 1. Changes in platelets levels after sirolimus therapy in primary antiphospholipid syndrome patients with thrombocytopenia, (A) platelet count of individual patient during the whole follow-up, (B) Median platelet count of included patients during the first six months. Disclosure of Interests None declared
AB1276 EVALUATION OF DRUG-FREE REMISSION RATES IN IDIOPATHIC GRANULOMATOUS MASTITIS
Authors: M. N. Kaya, Ö. Kiliç, E. Tekgoz, S. Colak, M. Çinar, S. Yilmaz
Journal: Annals of the Rheumatic Diseases (2022)

Background Idiopathic granulomatous mastitis (IGM) is a rare inflammatory breast disease. There is no clear consensus on its treatment yet (1). Objectives The aim of the study was to evaluate the rates of drug-free remission of the patients with IGM in a period of three-year follow-up. Methods A total of 76 patients who were followed-up with biopsy proven IGM, between February 2011 and November 2021 in rheumatology outpatient clinic of Gulhane Training and Research Hospital, were evaluated retrospectively. To analyze long-term outcomes, 55 patients who were followed up for 3 years were included in the study. Data regarding the demographic and clinical characteristics of the patients were obtained from patients’ files. Results The study included 55 female patients with a mean age of 36.8 ± 6.3 years. Forty-nine (89.1%) patients received immunosuppressive treatment, one (1.8%) patient received postoperative immunosuppressive treatment, 3 (5.4%) patients had immunosuppressive treatment due to recurrence after surgery, and 1 (1.8%) patient underwent only surgery. One (1.8%) patient had no treatment for IGM. Patients who received immunosuppressive drugs for initial treatment, 38 (69.1%) received methotrexate (MTX) and corticosteroids (CS), 7 (13.2%) received azathioprine (AZA) and CS, 3 (5.6%) received only CS and 1 (1.8%) received cyclosporine A (CsA) and CS. Four (7.2 %) patients had received MTX after surgery. At 3-year follow-up 54 (98.1%) patients were in drug-free remission. The median duration of drug-free remission in patients receiving MTX plus CS, CS, and azathioprine plus CS was 19.7, 32.9, and 14.7 months, respectively. One patient who received CsA plus CS was in drug-free remission for 28.3 months. The median duration of treatment with combination of CS and other immunosuppressives was 6.7 months. The median duration of immunosuppressive treatment was 15.8 months (Table 1). Recurrence was observed in 4 (80%) patients who did not receive immunosuppressive therapy after surgery. Three (75%) of these patients received MTX due to recurrence, and remission was achieved. Table 1. Duration of immunosuppressive treatment and drug-free remission of the patients Treatment Duration of immunosuppressives, (n=53) Duration of drug-free remission, (n=54) Only corticosteroids (month)* 4.6 (2.9-5.8) 32.9 (32.4-33.4) Methotrexate (month)* 19.7 (2.8-32.4) 19.7 (2.7-32.4) Azathioprine (month)* 16.2 (11.0-30.1) 14.7 (8.8-22.9) Cyclosporine (month) 7.6 28.3 Total (month)* 15.8 (2.9-34.3) 21.2 (2.7-36.6) * Variables as median, (minimum - maximum) Conclusion Immunosuppressives provide a remarkably high sustained remission and maintain a longer drug-free remission in patients with IGM. References [1]Tekgöz E, Çolak S, Çinar M, Yilmaz S. Treatment of idiopathic granulomatous mastitis and factors related with disease recurrence. Turk J Med Sci. (2020) 50: 1380-1386. Disclosure of Interests None declared
Michael Servetus, Doctor of Medicine—Reply
Authors: Arman Zargaran
Journal: JAMA Cardiology (2022)

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AB0692 Predictors of iloprost infusion tolerance in patients with systemic sclerosis
Authors: R. Bixio, E. Bertoldo, A. Giollo, G. Adami, A. Morciano, D. Bertelle, I. Gavioli, G. Orsolini, O. Viapiana, M. Rossini
Journal: Annals of the Rheumatic Diseases (2022)

Background Systemic Sclerosis (SSc) is an autoimmune disease characterized by vasospasm and microvascular involvement. Iloprost (ILO), a prostaglandin analogous, is used for the treatment of SSc-related Raynaud’s Phenomenon and digital ulcers. The indicated dosage is 0-5-2 ng/kg/min for 6-8 hours and the maximum dose is decided upon the patient’s tolerance. Objectives Our study aims to analyse ILO infusion tolerance and possible predictive factors in patients with SSc. Methods We evaluated patients with SSc beginning ILO iv treatment between 2004 and 2021. We assessed the maximum tolerated ILO iv infusion rate, the incidence of adverse events (AEs) and the need for symptomatic therapy during the dose-finding sessions. We collected relevant demographic and medical data at the beginning of ILO iv treatment. Statistical analysis were performed to assess possible predictors of maximum tolerated ILO infusion rate and AEs. Results We retrospectively analysed 113 patients. The median ILO infusion rate at the end of the dose-finding process was 0.88 ng/kg/min (IQR 0.37). We found a significant inverse correlation between ILO infusion rate and body mass index (BMI) at the beginning of treatment. BMI was negatively associated with ILO infusion rate (β -0.29, p = 0.001) after correction for relevant confounding factors. Subjects in the upper BMI tertile (BMI above 25) had a lower tolerance to ILO compared with subjects in the lower BMI tertile BMI below 22 (p=0.002). Disease pattern, disease duration, age at the onset of disease, mean blood pressure, gender, smoking habits, combination therapy with calcium channel blocker or endothelin inhibitors were not predictors of ILO tolerance. AEs during ILO titration occurred in 47.8% of patients, of whom 22.2% presented concomitant hypotension. The most common AEs were headache, nausea, vomiting, diarrhoea, oedema, hypotension, and symptomatic therapy was needed in half of the patients at least once. Overweight patients (BMI &gt;26) presented a 13-fold increased risk of developing AEs during ILO titration (adjusted odd ratio 13.979 95% CI 2.359-82.845). Conclusion Our study showed that only a higher BMI was associated with lower ILO infusion rate tolerance and higher AEs rate, underlying a possible BMI-dependent endothelial dysfunction possibly mediated by endothelin receptor expression. Individual ILO regimens still need to be tailored to the patient. Disclosure of Interests None declared
AB0734 The dynamics of lung function in patients with systemic scleroderma associated with interstitial lung disease during a three-year follow-up period.
Authors: M. Starovoytova, O. Desinova, L. P. Ananyeva, O. Koneva, L. Garzanova, O. Ovsyannikova, R. Shayakhmetova, A. Khelkovskaia-Sergeeva
Journal: Annals of the Rheumatic Diseases (2022)

Background Nowadays ILD is one of the most common manifestations of SSc and the leading cause of death of patients. 25% to 30% of patients develop progressive ILD. Objectives To assess the course and outcomes of interstitial lung disease (ILD) in systemic sclerosis (SSc) based on lung function after three years of follow-up. Methods The study included 82 patients with SSc associated with ILD. There were 70 (85%) women and 12 (15%) men, whose average age was 49.86±12.30 years, 49 (60%) patients with limited SSc, 24 (29%) patients with diffuse SSD, 7 (9%) patients with overlap syndrome; median disease duration was 7 (4;11) years. The great majority of patients had a chronic course of the disease. The patients had systemic manifestations, vascular disorders and lesions of the musculoskeletal system. According to the results of CT scan of the thoracic organs, 28% of patients had more than 20% of pulmonary involvement. All patients took glucocorticoids (GCs); the average dose of prednisone was 8.6±4.6 mg. 50 (61%) patients took immunosuppressants (IS). The diagnosis was set according to ACR/EULAR criteria. The patients were examined twice in accordance with generally accepted approaches. To identify and assess the dynamics of ILD, there was used high-resolution computed tomography (HRCT) Their lung function was assessed by data obtained due to spirometry (in particular, forced vital capacity, FVC) and diffusing capacity of the lungs (DCL); Doppler echocardiography was also conducted. Results In the group of patients with SSc, a significant improvement was noticed in some indicators demonstrating the peculiar manifestations of the disease. Therefore, skin induration (a decrease in skin score) decreased from the initial 5.8±5.2 to an average of 4.6±3.9 points after three years, p=0.0001. Functional capacities of the lungs and heart did not deteriorate. There was a trend towards an increase in FVC by 5.7% (from 91.8±19.1 to 96.15±18.26, respectively). However, these data were not clinically significant. Systolic pulmonary artery pressure (sPAP) also remained stable, mm Hg (31.83±8.10 and 33.57±9.03, respectively), indirectly indicating the absence of progression in pulmonary involvement. These positive alterations were the basis for reducing the daily dose of GCs in some patients. The reduction in dose of GCs was small but statistically significant (8.64±4.58 and 7.86±3.33, respectively, p=0.007). Conclusion Therefore, due to the study, stabilization of lung function and the absence of progression in the SSc-ILD group were noticed, which emphasizes the importance of continuous monitoring and follow-up of patients and continuation of therapy. Disclosure of Interests None declared
Strengthening Food and Nutrition Security to Promote Public Health in the United States: A Position Paper From the American College of Physicians
Authors: Josh Serchen, Omar Atiq, David Hilden, Josh Serchen, Omar Atiq, David Hilden, Micah Beachy, Heather Brislen, William Curry, Lee Engel, Matthew Hollon, Suja Mathew, Pranav Mellacheruvu, Ankita Sagar, Christiana Shoushtari, Molly Southworth, Michael Tan
Journal: Annals of Internal Medicine (2022)

Food insecurity functions as a social driver of health, directly negatively impacting health status and outcomes, which can further negatively impact employment and income and increase medical expenditures-all of which exacerbates food insecurity. Progress in meaningfully reducing the food-insecurity rate has stalled in recent years. Although rates have decreased since their peak during the Great Recession, these gains have been reversed by the economic implications of the COVID-19 pandemic. As the federal government is the largest provider of food assistance, there is much potential in better leveraging nutrition assistance programs like the Supplemental Nutrition Assistance Program (SNAP) and the Child Nutrition Programs to increase access to healthful foods and improve public health. However, these programs face many funding challenges and internal shortcomings that create uncertainties and prevent maximal effect. Physicians and other medical professionals also have a role in improving nutritional health by screening for food insecurity and serving as connectors between patients, community organizations, and government services. Governments and payers must support these efforts by providing sufficient resources to practices to fulfill this role. In this position paper, the American College of Physicians (ACP) offers several policy recommendations to strengthen the federal food-insecurity response and empower physicians and other medical professionals to better address those social drivers of health occurring beyond the office doors.
AB0625 Association between Cytomegalovirus Reactivation and Renal Prognosis during Remission Induction Therapy for ANCA-Associated Vasculitis
Authors: K. Kawamori, N. Oguro, T. Kida, S. Omura, D. Nakagomi, K. Masatoshi, N. Takizawa, A. Nomura, K. Yuji, N. Kondo, Y. Yasuhiko, T. Yanagida, K. Endo, S. Hirata, K. Kawahata, K. Matsui, T. Takeuchi, K. Ichinose, M. Kato, R. Yanai, Y. Matsuo, Y. Shimojima, R. Nishioka, A. Yamasaki, T. Takata, T. Ito, M. Moriyama, A. Takatani, Y. Miyawaki, Y. Kawahito, T. Ito-Ihara, T. Kawaguchi, N. Yajima
Journal: Annals of the Rheumatic Diseases (2022)

Background Cytomegalovirus (CMV) has been associated with atherosclerosis in patients with chronic renal failure, and may cause secondary nephrotic syndrome. Therefore, we hypothesized that the reactivation of CMV by immunosuppressive therapy in patients with vasculitis may affect renal function. Objectives The purpose of this study was to investigate relationships between CMV infection and renal function during ANCA-associated vasculitis remission induction therapy. Methods This retrospective cohort study enrolled microscopic polyangiitis (MPA), granulomatosis with polyangiitis (GPA), and eosinophilic granulomatosis with polyangiitis patients at 25 sites in Japan who had a first or severe relapse between January 2017 and June 2020. Of these, patients with MPA or GPA who had a positive renal lesion score on BVAS (version 3) at baseline, or vasculitis findings on renal biopsy, CMV assayed by 48 weeks of treatment, were included. Patients were divided into two groups based on the presence or absence of a positive CMV antigen test during the remission induction phase (0–48 weeks of treatment). Outcomes were the rate of change in estimated glomerular filtration rate (eGFR) at 48 weeks after initiation of treatment in both groups, as determined by (eGFR at 48 weeks - eGFR at the initiation of treatment)/eGFR at the initiation of treatment; where lower values were associated with worse renal function. General linear models adjusted for age, gender, presence of diabetes or chronic kidney disease, and the use of rituximab or cyclophosphamide were generated. Results A total of 387 patients had CMV antigen measured during ANCA-associated vasculitis treatment, of which 164 had renal involvement and eGFR measured at 48 weeks. Seventy-seven (47.0%) were male and the median age was 75 years (range 69–80 years). CMV reactivation was observed in 44 patients (26.8%). The beta coefficient of multiple regression analysis with CMV positive as 1 and negative as 0 was 0.08 (95% confidence interval -0.13 to 0.29) (p = 0.47). The rate of change in eGFR was higher in the CMV positive group, but not statistically significantly. Conclusion Contrary to our hypothesis, renal prognoses tended to be better when CMV reactivation was observed. The patients in the CMV reactivation group may have been treated more aggressively, and some patients with a poor prognosis who were not followed up for 48 weeks dropped out. Further research investigating the adjustment of treatment methods is required. Disclosure of Interests None declared
Therapeutic drug monitoring-based precision dosing of oral targeted therapies in oncology: a prospective multicenter study
Authors: S.L. Groenland, R.A.G. van Eerden, K. Westerdijk, M. Meertens, S.L.W. Koolen, D.J.A.R. Moes, N. de Vries, H. Rosing, H. Otten, A.J.E. Vulink, I.M.E. Desar, A.L.T. Imholz, H. Gelderblom, N.P. van Erp, J.H. Beijnen, R.H.J. Mathijssen, A.D.R. Huitema, N. Steeghs
Journal: Annals of Oncology (2022)